Cyclization silicon-tethered

Skrydstrup, Beau and co-workers122 have adapted Stork s method to the SmI2-reduction of glycosyl pyridyl sulfones bearing a silicon-tethered unsaturated group at HO-C(2). An example is shown with the synthesis of methyl a-C-zso-maltoside 172 from alkyne 170 via the 5-exo-dig radical cyclization of 171 (Scheme 56).144... 

J. C. Lopez, A. M. Gomez, and B. Fraser-Reid, Silicon-tethered radical cyclization and intramolecular Diels-Alder strategies are combined to provide a ready route to highly functionalized decalins, J. Chem. Soc. Chem. Comtmm. p. 762 (1993). 

Fraser-Reid s stereocontrolled synthesis of the Woodward reserpine precursor 195 relied upon a tandem 5-exol6-exo radical cyclization of pyranose-derived dienes [76-77]. As outlined in Scheme 36, a,P-unsaturated ester 188 was prepared by free radical coupling of iodide 187 with a tin acrylate. After hydrolysis of 188 (MeONa, MeOH, 100%) to give primary alcohol 189, the silicon tethered diene 190 was installed by silylation. Treatment of 190 with n-BujSnH led to the desired cage molecule 192 in high yield via a 5-exo-trig cyclization to intermediate 191 followed by a 6-exo cyclization. Tamao oxidation of tricycle 192 led to diol... 

Curran and co-workers have explored the use of silicon tethers to carry out these reactions. They have successfully demonstrated the 1,5 and 1,6 translocation of a radical that goes on to do intramolecular cyclization reactions. This method was used to synthesize natural product such as crinipellin A22 and 2-(o)-(2-bromoaryl)dimethylsilyl-a-methyl-D-mannopyranoside.24 One of the nice benefits to the use of silicon tethers is that they serve as a hydroxyl-protecting group before and after the reaction is performed. 

Despite the development of various intermolecular radical addition methods, those studies have rarely accommodated additional functionality, our discovery of the manganese-mediated photolysis conditions notwithstanding. Prior to that discovery, we began to elaborate an alternative strategy which employs temporary tethers ([115, 116] reviews of silicon-tethered reactions [117-120]) (silyl ether or acetal linkages) linking radical and acceptor. In this scenario the C-C bond is constructed via cyclization, in which internal conformational constraints can control diaster-eoselectivity. The tether itself would be converted to useful functionality upon cleavage, and once the tether is cleaved the net result may be considered as formal acyclic stereocontrol. ... 

A diastereoselective formal addition of a 7ra i-2-(phenylthio)vmyl moiety to a-hydroxyhydrazones through a radical pathway is shown in Scheme 2.29. To overcome the lack of a viable intermolecular vinyl radical addition to C=N double bonds, not to mention a reaction proceeding with stereocontrol, this procedure employs a temporary silicon tether, which is used to hold the alkyne unit in place so that the vinyl radical addition could proceed intramolecularly. Thus, intermolecular addition of PhS" to the alkyne moiety in the chiral alkyne 161 leads to vinyl radical 163, which cyclizes in a 5-exo fashion, according to the Beckwith-Houk predictions, to give aminyl radical 164 with an a 7z-arrangement between the ether and the amino group. Radical reduction and removal of the silicon tether without prior isolation of the end product of the radical cyclization cascade, 165, yields the a-amino alcohol 162. This strategy, which could also be applied to the diastereoselective synthesis of polyhydroxylated amines (not shown), can be considered as synthetic equivalent of an acetaldehyde Mannich reaction with acyclic stereocontrol. 

Our strategy for the Smij-promoted synthesis of l,2-cis-C-glycosides is illustrated in Figure 3. It was assumed that one-electron transfer to the LUMO of the aryl sulfone group in A would result in concomitant cleavage of the C1 -S bond liberating an anomeric radical intermediate, as previously observed in the reductive lithiation of glycosyl phenyl sulfones." If 5-exo cyclization onto the silicon-tethered alkene/alkyne is substantially favored over a second electron transfer from Smij, then the exocyclic carbon radical B would ultimately be formed. On the other hand, reduction of the Cl-radical by... 

Analogously, intramolecular hydrosilation reactions have been carried out with alkenes cyclization of alkenyloxy-silanes catalyzed by thiols <1998J(P1)467> and by Pt <1996TL827> has been described. In addition, intramolecular temporary silicon-tethered rhodium-catalyzed [4- -2- -2]-cycloisomerization reactions have been carried out by Evans and Bawn (Equation 50) <2004JA11150>. 

The advantage of a silicon tether is illustrated further by reaction of lb with (E)-(chlorodimethylsilyl)acrylate 6 to provide 7. This cyclizes to a single, endo-adduct 8, which can be converted to 9 and 10 as shown. 

A highly general procedure relies on the use of a silicon tethered radical cyclization process to provide for introduction of a hydroxymethyl substituent using the Tamao conditions.33 38 Pioneered by Nishiyama39 the synthesis of regioisomeric diols, as in 33, from readily available ally silyl ethers, such as 31, was achieved via radical cyclization and oxidization. The predominance of the 5-exo cyclization is further demonstrated by the formation of 36 by this same process. 

Scheme 15. Preparation of C-disaccharides via Sm -induced radical cyclization using silicon tethering...

Scheme 10-47 Crimmins and O Mahony used a silicon-tethered radical cyclization in a synthesis of talaromycin A.

Scheme 10-106 Silicon-tethered ene cyclization is highly stereoselective.

Olefins andAlkynes. The increased scope of the silicon tether in radical chemistry, which is still the most important reactivity allowed by the (bromomethyl)dimethylsilane moiety, has been reviewed. Some authors have again illustrated the synthetic interest of Nishiyama-Stork radical cyclizations of allylic (bromomethyl)dimethylsilyl ethers. Jenkins achieved stereoselective cyclizations on a fused cyclopentanol, while Herdewijn prepared pyranosyl nucleosides. Starting from /-substituted... 

Silicon-tethered Ene Reactions. Silicon-tethered cyclization reactions have been widely utilized because of the ease of formation and removal of the temporary silicon tether and the ability of organosilicon compounds to tolerate many commonly used organic transformations. One example involves the ene reaction of a-(prenyl)dialkylsilyloxy aldehydes (eq 13). A 1,2-diol (39) can... 

Vinyl groups have also been transferred to quaternary carbons using the vinyl silicon tether strategy. The vinylsiloxy ethers 21 were made by the reaction of the corresponding alcohols in DMF or DCM with chlorodimethylvinylsilane in the presence of pyridine or imidazole. They were subjected to radical reaction conditions using triethylborane to initiate the intramolecular cyclization followed by acid treatment to form the elimination products 22 favoring the 2,3-5 yw-diastereomer in good yields (eq 11). ... 

Silicon has also been employed as a tether for directing ringclosing metathesis (RCM) reactions. The RCM precursors 38 were generated by attachment of chlorodimethylvinylsilane to alkenyl alcohols. An olefin metathesis reaction using Schrock s catalyst provided the cyclized products 39 in excellent yields (eq 18). Although Grubbs catalyst had been successfully employed in the case of allylsiloxy dienes, Schrock s catalyst resulted in better yields in the case of the vinylsiloxy dienes 39. Oxidative cleavage of the silicon tether was then used to provide acyclic hydroxyaldehydes. 

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